Any feedback?
Information on EC 3.5.1.98 - histone deacetylase and Organism(s) Mus musculus and UniProt Accession P70288
for references in articles please use BRENDA:EC3.5.1.98Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
EC Tree
3.5.1.98 histone deacetylaseIUBMB Comments
A class of enzymes that remove acetyl groups from N6-acetyl-lysine residues on a histone. The reaction of this enzyme is opposite to that of EC 2.3.1.48, histone acetyltransferase. Histone deacetylases (HDACs) can be organized into three classes, HDAC1, HDAC2 and HDAC3, depending on sequence similarity and domain organization. Histone acetylation plays an important role in regulation of gene expression. In eukaryotes, HDACs play a key role in the regulation of transcription and cell proliferation . May be identical to EC 3.5.1.17, acyl-lysine deacylase.
Specify your search results
Word Map
- 3.5.1.98
- hdacs
- chromatin
- deacetylases
-
trichostatin
-
deacetylation
-
hydroxamic
-
valproic
- saha
- acetyltransferase
- leukemia
- butyrate
-
hyperacetylation
- methyltransferase
- vorinostat
- repressor
- lymphoma
- microtubule
- cyclin
- sirtuins
- nucleosome
- t-cells
-
transactivation
-
caspase
- bcl-2
- metastasis
- myeloid
- proteasome
-
hypermethylation
- tumorigenesis
- cardiac
- sirt1
- neurodegenerative
- hematological
- prostate
-
demethylation
-
antiproliferative
-
corepressors
- sirnas
- cpg
-
non-histone
- 5-aza-2'-deoxycytidine
- valproate
- medicine
-
polycomb
- bortezomib
- dnmt3a
- heterochromatin
-
creb-binding
-
epigenome
- drug development
-
coactivator
-
relapsed
The taxonomic range for the selected organisms is: Mus musculus
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
Reaction Schemes
hydrolysis of an N6-acetyl-lysine residue of a histone to yield a deacetylated histone
Synonyms
histone deacetylase, hdac1, hdac6, hdac2, hdac3, hdac4, hdac5, hdac8, hdac9, hdac7, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
deacetylation
SYSTEMATIC NAME
IUBMB Comments
histone amidohydrolase
A class of enzymes that remove acetyl groups from N6-acetyl-lysine residues on a histone. The reaction of this enzyme is opposite to that of EC 2.3.1.48, histone acetyltransferase. Histone deacetylases (HDACs) can be organized into three classes, HDAC1, HDAC2 and HDAC3, depending on sequence similarity and domain organization. Histone acetylation plays an important role in regulation of gene expression. In eukaryotes, HDACs play a key role in the regulation of transcription and cell proliferation [4]. May be identical to EC 3.5.1.17, acyl-lysine deacylase.
CAS REGISTRY NUMBER
COMMENTARY
9076-57-7
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
N-acetyl-lysine-histone H3 + H2O
acetate + histone H3
-
-
individual lysine residues in the H3 tail are deacetylated at similar rates
-
?
N-acetyl-lysine-histone H4 + H2O
acetate + histone H4
-
-
rate of deacetylation is not uniform. H4 K5 is deacetylated first, followed by K8, K12 and K16. The specificity of deacetylation and the histone-binding preference of transcriptional co-repressors N-CoR/SMRT match each other, rate of deacetylation by isoform HDAC3 is not uniform. H4 K5 is deacetylated first, followed by K8, K12 and K16. The specificity of deacetylation and the histone-binding preference of transcriptional co-repressors N-CoR/SMRT match each other
-
?
additional information
?
-
-
histone deacetylases regulate the expression of HoxA9, which acts as a master switch to regulate the expression of prototypical endothelial-committed genes such as endothelial nitric oxide synthase, VE-cadherin, VEGF-R2, and mediates the shear stress-induced maturation of endothelial cells
-
-
?
additional information
?
-
HDAC7 physically binds to PLZF and modulates its transcriptional activity. PLZF belongs to the BTB-ZF family of transcription factors
-
-
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
N-acetyl-lysine-histone H4 + H2O
acetate + histone H4
-
-
rate of deacetylation is not uniform. H4 K5 is deacetylated first, followed by K8, K12 and K16. The specificity of deacetylation and the histone-binding preference of transcriptional co-repressors N-CoR/SMRT match each other
-
?
additional information
?
-
-
histone deacetylases regulate the expression of HoxA9, which acts as a master switch to regulate the expression of prototypical endothelial-committed genes such as endothelial nitric oxide synthase, VE-cadherin, VEGF-R2, and mediates the shear stress-induced maturation of endothelial cells
-
-
?
additional information
?
-
HDAC7 physically binds to PLZF and modulates its transcriptional activity. PLZF belongs to the BTB-ZF family of transcription factors
-
-
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(2E)-N-(2-aminophenyl)-3-(4-{1-[(2-hydroxyethyl)amino]-2-oxo-2-[4-(trifluoromethyl)anilino]ethyl}phenyl)prop-2-enamide
-
(2E)-N-(2-aminophenyl)-3-(4-{1-[(3S)-3-(dimethylamino)pyrrolidin-1-yl]-2-oxo-2-[4-(trifluoromethyl)anilino]ethyl}phenyl)prop-2-enamide
-
(2E)-N-(2-aminophenyl)-3-[4-(1-{[2-(morpholin-4-yl)ethyl]amino}-2-oxo-2-[4-(trifluoromethyl)anilino]ethyl)phenyl]prop-2-enamide
-
(2E)-N-(2-aminophenyl)-3-{4-[2-(4-bromoanilino)-1-(3-hydroxypyrrolidin-1-yl)-2-oxoethyl]phenyl}prop-2-enamide
-
(3R)-4-{4-[(1E)-3-(2-aminoanilino)-3-oxoprop-1-en-1-yl]-2-fluorophenyl}-N-(4-chlorophenyl)-1-methylpyrrolidine-3-carboxamide
-
(3R)-4-{4-[(1E)-3-(2-aminoanilino)-3-oxoprop-1-en-1-yl]phenyl}-1-benzyl-N-(4-chlorophenyl)pyrrolidine-3-carboxamide
-
(3R)-4-{4-[(1E)-3-(2-aminoanilino)-3-oxoprop-1-en-1-yl]phenyl}-1-methyl-N-(3-methylphenyl)pyrrolidine-3-carboxamide
-
(3R)-4-{4-[(1E)-3-(2-aminoanilino)-3-oxoprop-1-en-1-yl]phenyl}-1-methyl-N-(4-methylphenyl)pyrrolidine-3-carboxamide
-
(3R)-4-{4-[(1E)-3-(2-aminoanilino)-3-oxoprop-1-en-1-yl]phenyl}-1-methyl-N-(6-methylpyridin-3-yl)pyrrolidine-3-carboxamide
-
(3R)-4-{4-[(1E)-3-(2-aminoanilino)-3-oxoprop-1-en-1-yl]phenyl}-1-methyl-N-(piperidin-1-yl)pyrrolidine-3-carboxamide
-
(3R)-4-{4-[(1E)-3-(2-aminoanilino)-3-oxoprop-1-en-1-yl]phenyl}-1-methyl-N-(propan-2-yl)pyrrolidine-3-carboxamide
-
(3R)-4-{4-[(1E)-3-(2-aminoanilino)-3-oxoprop-1-en-1-yl]phenyl}-1-methyl-N-(pyridin-2-yl)pyrrolidine-3-carboxamide
-
(3R)-4-{4-[(1E)-3-(2-aminoanilino)-3-oxoprop-1-en-1-yl]phenyl}-1-methyl-N-(pyridin-3-yl)pyrrolidine-3-carboxamide
-
(3R)-4-{4-[(1E)-3-(2-aminoanilino)-3-oxoprop-1-en-1-yl]phenyl}-1-methyl-N-(pyridin-4-yl)pyrrolidine-3-carboxamide
-
(3R)-4-{4-[(1E)-3-(2-aminoanilino)-3-oxoprop-1-en-1-yl]phenyl}-1-methyl-N-phenylpyrrolidine-3-carboxamide
-
(3R)-4-{4-[(1E)-3-(2-aminoanilino)-3-oxoprop-1-en-1-yl]phenyl}-1-methyl-N-[4-(propan-2-yl)phenyl]pyrrolidine-3-carboxamide
-
(3R)-4-{4-[(1E)-3-(2-aminoanilino)-3-oxoprop-1-en-1-yl]phenyl}-1-methyl-N-[4-(trifluoromethyl)phenyl]pyrrolidine-3-carboxamide
-
(3R)-4-{4-[(1E)-3-(2-aminoanilino)-3-oxoprop-1-en-1-yl]phenyl}-N-(2,4-difluorophenyl)-1-methylpyrrolidine-3-carboxamide
-
(3R)-4-{4-[(1E)-3-(2-aminoanilino)-3-oxoprop-1-en-1-yl]phenyl}-N-(2-chloro-4-fluorophenyl)-1-methylpyrrolidine-3-carboxamide
-
(3R)-4-{4-[(1E)-3-(2-aminoanilino)-3-oxoprop-1-en-1-yl]phenyl}-N-(2-fluorophenyl)-1-methylpyrrolidine-3-carboxamide
-
(3R)-4-{4-[(1E)-3-(2-aminoanilino)-3-oxoprop-1-en-1-yl]phenyl}-N-(3,4-dichlorophenyl)-1-methylpyrrolidine-3-carboxamide
-
(3R)-4-{4-[(1E)-3-(2-aminoanilino)-3-oxoprop-1-en-1-yl]phenyl}-N-(3,4-difluorophenyl)-1-methylpyrrolidine-3-carboxamide
-
(3R)-4-{4-[(1E)-3-(2-aminoanilino)-3-oxoprop-1-en-1-yl]phenyl}-N-(3-bromo-4-fluorophenyl)-1-methylpyrrolidine-3-carboxamide
-
(3R)-4-{4-[(1E)-3-(2-aminoanilino)-3-oxoprop-1-en-1-yl]phenyl}-N-(3-chloro-4-fluorophenyl)-1-methylpyrrolidine-3-carboxamide
-
(3R)-4-{4-[(1E)-3-(2-aminoanilino)-3-oxoprop-1-en-1-yl]phenyl}-N-(3-chlorophenyl)-1-methylpyrrolidine-3-carboxamide
-
(3R)-4-{4-[(1E)-3-(2-aminoanilino)-3-oxoprop-1-en-1-yl]phenyl}-N-(3-fluorophenyl)-1-methylpyrrolidine-3-carboxamide
-
(3R)-4-{4-[(1E)-3-(2-aminoanilino)-3-oxoprop-1-en-1-yl]phenyl}-N-(3-methoxyphenyl)-1-methylpyrrolidine-3-carboxamide
-
(3R)-4-{4-[(1E)-3-(2-aminoanilino)-3-oxoprop-1-en-1-yl]phenyl}-N-(4-bromophenyl)-1-methylpyrrolidine-3-carboxamide
-
(3R)-4-{4-[(1E)-3-(2-aminoanilino)-3-oxoprop-1-en-1-yl]phenyl}-N-(4-chloro-3-methylphenyl)-1-methylpyrrolidine-3-carboxamide
-
(3R)-4-{4-[(1E)-3-(2-aminoanilino)-3-oxoprop-1-en-1-yl]phenyl}-N-(4-chlorophenyl)-1-(2,2,2-trifluoroethyl)pyrrolidine-3-carboxamide
-
(3R)-4-{4-[(1E)-3-(2-aminoanilino)-3-oxoprop-1-en-1-yl]phenyl}-N-(4-chlorophenyl)-1-(2,2-difluoroethyl)pyrrolidine-3-carboxamide
-
(3R)-4-{4-[(1E)-3-(2-aminoanilino)-3-oxoprop-1-en-1-yl]phenyl}-N-(4-chlorophenyl)-1-(2,2-dimethylpropyl)pyrrolidine-3-carboxamide
-
(3R)-4-{4-[(1E)-3-(2-aminoanilino)-3-oxoprop-1-en-1-yl]phenyl}-N-(4-chlorophenyl)-1-(2-fluoroethyl)pyrrolidine-3-carboxamide
-
(3R)-4-{4-[(1E)-3-(2-aminoanilino)-3-oxoprop-1-en-1-yl]phenyl}-N-(4-chlorophenyl)-1-(2-hydroxy-2-methylpropyl)pyrrolidine-3-carboxamide
-
(3R)-4-{4-[(1E)-3-(2-aminoanilino)-3-oxoprop-1-en-1-yl]phenyl}-N-(4-chlorophenyl)-1-(2-hydroxyethyl)pyrrolidine-3-carboxamide
-
(3R)-4-{4-[(1E)-3-(2-aminoanilino)-3-oxoprop-1-en-1-yl]phenyl}-N-(4-chlorophenyl)-1-(2-methoxyethyl)pyrrolidine-3-carboxamide
-
(3R)-4-{4-[(1E)-3-(2-aminoanilino)-3-oxoprop-1-en-1-yl]phenyl}-N-(4-chlorophenyl)-1-(3-hydroxy-2,2-dimethylpropyl)pyrrolidine-3-carboxamide
-
(3R)-4-{4-[(1E)-3-(2-aminoanilino)-3-oxoprop-1-en-1-yl]phenyl}-N-(4-chlorophenyl)-1-(cyanomethyl)pyrrolidine-3-carboxamide
-
(3R)-4-{4-[(1E)-3-(2-aminoanilino)-3-oxoprop-1-en-1-yl]phenyl}-N-(4-chlorophenyl)-1-(oxan-4-yl)pyrrolidine-3-carboxamide
-
(3R)-4-{4-[(1E)-3-(2-aminoanilino)-3-oxoprop-1-en-1-yl]phenyl}-N-(4-chlorophenyl)-1-(propan-2-yl)pyrrolidine-3-carboxamide
-
(3R)-4-{4-[(1E)-3-(2-aminoanilino)-3-oxoprop-1-en-1-yl]phenyl}-N-(4-chlorophenyl)-1-(pyrimidin-2-yl)pyrrolidine-3-carboxamide
-
(3R)-4-{4-[(1E)-3-(2-aminoanilino)-3-oxoprop-1-en-1-yl]phenyl}-N-(4-chlorophenyl)-1-cyclobutylpyrrolidine-3-carboxamide
-
(3R)-4-{4-[(1E)-3-(2-aminoanilino)-3-oxoprop-1-en-1-yl]phenyl}-N-(4-chlorophenyl)-1-ethylpyrrolidine-3-carboxamide
-
(3R)-4-{4-[(1E)-3-(2-aminoanilino)-3-oxoprop-1-en-1-yl]phenyl}-N-(4-chlorophenyl)-1-methylpyrrolidine-3-carboxamide
-
(3R)-4-{4-[(1E)-3-(2-aminoanilino)-3-oxoprop-1-en-1-yl]phenyl}-N-(4-cyanophenyl)-1-methylpyrrolidine-3-carboxamide
-
(3R)-4-{4-[(1E)-3-(2-aminoanilino)-3-oxoprop-1-en-1-yl]phenyl}-N-(4-cyclopropylphenyl)-1-methylpyrrolidine-3-carboxamide
-
(3R)-4-{4-[(1E)-3-(2-aminoanilino)-3-oxoprop-1-en-1-yl]phenyl}-N-(4-fluoro-3-methylphenyl)-1-methylpyrrolidine-3-carboxamide
-
(3R)-4-{4-[(1E)-3-(2-aminoanilino)-3-oxoprop-1-en-1-yl]phenyl}-N-(4-fluorophenyl)-1-methylpyrrolidine-3-carboxamide
-
(3R)-4-{4-[(1E)-3-(2-aminoanilino)-3-oxoprop-1-en-1-yl]phenyl}-N-(4-methoxyphenyl)-1-methylpyrrolidine-3-carboxamide
-
(3R)-4-{4-[(1E)-3-(2-aminoanilino)-3-oxoprop-1-en-1-yl]phenyl}-N-(5-chloropyridin-2-yl)-1-methylpyrrolidine-3-carboxamide
-
(3R)-4-{4-[(1E)-3-(2-aminoanilino)-3-oxoprop-1-en-1-yl]phenyl}-N-cyclopentyl-1-methylpyrrolidine-3-carboxamide
-
(3R)-4-{4-[(1E)-3-(2-aminoanilino)-3-oxoprop-1-en-1-yl]phenyl}-N-cyclopropyl-1-methylpyrrolidine-3-carboxamide
-
(3R)-4-{4-[(1E)-3-(2-aminoanilino)-3-oxoprop-1-en-1-yl]phenyl}-N~3~-(4-chlorophenyl)-N~1~,N~1~-diethylpyrrolidine-1,3-dicarboxamide
-
(3R)-4-{4-[(1E)-3-(2-aminoanilino)-3-oxoprop-1-en-1-yl]phenyl}-N~3~-(4-chlorophenyl)-N~1~-ethylpyrrolidine-1,3-dicarboxamide
-
(3R)-4-{5-[(1E)-3-(2-aminoanilino)-3-oxoprop-1-en-1-yl]pyrazin-2-yl}-N-(4-chlorophenyl)-1-methylpyrrolidine-3-carboxamide
-
(3R)-4-{5-[(1E)-3-(2-aminoanilino)-3-oxoprop-1-en-1-yl]pyridin-2-yl}-N-(4-chlorophenyl)-1-methylpyrrolidine-3-carboxamide
-
(3R)-4-{6-[(1E)-3-(2-aminoanilino)-3-oxoprop-1-en-1-yl]pyridazin-3-yl}-N-(4-chlorophenyl)-1-methylpyrrolidine-3-carboxamide
-
(3R)-4-{6-[(1E)-3-(2-aminoanilino)-3-oxoprop-1-en-1-yl]pyridin-3-yl}-N-(4-chlorophenyl)-1-methylpyrrolidine-3-carboxamide
-
(3R,4S)-4-{4-[(1E)-3-(2-aminoanilino)-3-oxoprop-1-en-1-yl]phenyl}-N-(4-chlorophenyl)-1-methylpyrrolidine-3-carboxamide
-
Butyrate
-
inhibition of histone deacetylases, results in down-regulation of HoxA9 expression
MS-275
-
inhibition of histone deacetylases, results in down-regulation of HoxA9 expression
suberoylanilide hydroxyamic acid
-
a specific inhibitor of zinc-dependent histone deacetylase activity. The compound directly induces p19INK4d expression in regenerating liver by increasing p19INK4d promoter-associated histone acetylation, molecular mechanisms by which the inhibitor delays liver regeneration exerting promoter-specific effects on histone acetylation during liver regeneration, overview
trichostatin A
-
inhibition of histone deacetylases, results in down-regulation of HoxA9 expression
additional information
pharmacokinetic optimization of class-selective histone deacetylase inhibitors and identification of associated candidate predictive biomarkers of hepatocellular carcinoma tumor response, structure-activity and structure-property relationships for trans-3,4-disubstituted pyrrolidine inhibitors, overview
-
additional information
-
pharmacokinetic optimization of class-selective histone deacetylase inhibitors and identification of associated candidate predictive biomarkers of hepatocellular carcinoma tumor response, structure-activity and structure-property relationships for trans-3,4-disubstituted pyrrolidine inhibitors, overview
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
in liver, class IIa HDACs HDAC4, 5, and 7, are phosphorylated and excluded from the nucleus by AMPK family kinases. In response to the fasting hormone glucagon, these HDACs are rapidly dephosphorylated and translocated to the nucleus where they associate with the promoters of gluconeogenic enzymes such as G6Pase. In turn, HDAC4/5 recruit HDAC3, which results in the acute transcriptional induction of these genes via deacetylation and activation of FOXO family transcription factors. Loss of class IIa HDACs in murine liver results in inhibition of FOXO target genes and lowers blood glucose, resulting in increased glycogen storage
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
subcellular localization of the class II HDACs 4, 5, and 7 is regulated by phosphorylation-dependent shuttling between the cytoplasmic and nuclear compartments
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
depleting maternal isozyme HDAC2 results in hyperacetylation of H4K16, while normal deacetylation of other lysine residues of histone H3 or H4 is observed, and defective chromosome condensation and segregation during oocyte maturation occurs in a subpopulation of oocytes, leading to increased incidence of aneuploidy likely accounts for the observed sub-fertility of mice harboring Hdac2-defective oocytes. The infertility of mice harboring Hdac1-/+/Hdac2-/- oocytes is attributed to failure of those few eggs that properly mature to metaphase II to initiate DNA replication following fertilization. Hdac1-/+/Hdac2-/- eggs are fertilized but fail to initiate DNA replication. The increased amount of acetylated H4K16 likely impairs kinetochore function in oocytes lacking isozyme HDAC2 because kinetochores in mutant oocytes are less able to form coldstable microtubule attachments and less CENP-A is located at the centromere. Phenotype, overview
physiological function
histone deacetylase 2 regulates chromosome segregation and kinetochore function via H4K16 deacetylation during oocyte maturation in mouse. HDAC2 is the major isozyme that regulates global histone acetylation during oocyte development and is largely responsible for the deacetylation of H4K16 during maturation. Histone deacetylation that occurs during oocyte maturation is critical for proper chromosome segregation
malfunction
physiological function
additional information
-
isoform-specific regulation of zinc-dependent histone deacetylase expression, subcellular localization, and activity in regenerating liver. The signals that regulate the PH-induced metabolic response to hepatic insufficiency are not downstream, but might be upstream, of the target of suberoylanilide hydroxyamic acid's anti-regenerative activity
malfunction
-
while brain development and adult stem cell fate are normal upon conditional deletion of HDAC2 or in mice lacking the catalytic activity of HDAC2, neurons derived from both zones of adult neurogenesis die at a specific maturation stage
malfunction
histone deacetylase 7 (HDAC7) controls the thymic effector programming of natural killer T (NKT) cells, and interference with this function contributes to tissue-specific autoimmunity. Gain of HDAC7 function in thymocytes blocks both negative selection and NKT development, and diverts Va14/Ja18 TCR transgenic thymocytes into a Tconv-like lineage. Conversely, HDAC7 deletion promotes thymocyte apoptosis and causes expansion of innate-effector cells, mechanisms, overview. Alteration of HDAC7 function dysregulates thymic innate effector programming and interferes with iNKT development. While the wild-type-derived population reconstitutes hepatic iNKT cells efficiently, HDAC7-DELTAP bone marrow makes almost no contribution to this compartment in the liver, where iNKT cells are most abundant. This is also true in the thymus and spleen, demonstrating that the abnormalities observed in the intact transgenic mice are due to a cell-autonomous mechanism. Analysis of effects of loss of HDAC7 in the thymus on these phenotypes. Deletion of Hdac7 does not result in expansion of NK1.1-expressing T-cells, but significant abnormalities in the effector programming of non-tetramer-reactive thymocytes are observed
physiological function
-
the catalytic function of HDAC2 is required in adult but not embryonic neurogenesis. HDAC2 is critically required to silence progenitor transcripts during neuronal differentiation of adult generated neurons
physiological function
-
in liver, class IIa HDACs HDAC4, 5, and 7, are phosphorylated and excluded from the nucleus by AMPK family kinases. In response to the fasting hormone glucagon, these HDACs are rapidly dephosphorylated and translocated to the nucleus where they associate with the promoters of gluconeogenic enzymes such as G6Pase. In turn, HDAC4/5 recruit HDAC3, which results in the acute transcriptional induction of these genes via deacetylation and activation of FOXO family transcription factors. Loss of class IIa HDACs in murine liver results in inhibition of FOXO target genes and lowers blood glucose, resulting in increased glycogen storage
physiological function
-
Sirt1 inhibits T cell activation by suppressing the transcription of Bcl2-associated factor 1, Bclaf1, a protein required for T cell activation. Sirt1-null T cells have increased acetylation of the histone 3 lysine 56 residue, H3K56, at the bclaf1 promoter, as well as increasing Bclaf1 transcription. Sirt1 binds to bclaf1 promoter upon T cell receptor/CD28 stimulation by forming a complex with histone acetyltransferase p300 and NF-kappaB transcription factor Rel-A. The recruitment of Sirt1, but not p300, requires Rel-A. Knockdown of Bclaf1 suppresses the hyperactivation observed in Sirt1-/- T cells. Therefore, Sirt1 negatively regulates T cell activation via H3K56 deacetylation at the promoter region to inhibit transcription of Bclaf1
physiological function
-
the enzyme activity promotes liver regeneration by regulating hepatocellular cell cycle progression at a step downstream of cyclin D1 induction
physiological function
histone deacetylase 7 mediates tissue-specific autoimmunity via control of innate effector function in invariant natural killer T cells. HDAC7 binds transcription factor promyelocytic leukemia zinc finger protein (PLZF, ZBTB16) and modulates PLZF-dependent transcription. Autoimmune diseases are observed in HDAC7 gain-of-function in mice. Association between HDAC7 and hepatobiliary autoimmunity. Tconv development is regulated by the class IIA histone deacetylase histone deacetylase 7 (HDAC7), a TCR signal-regulated corepressor abundantly expressed in thymocytes. The activity of HDAC7 is controlled by nuclear exclusion in response to phosphorylation of conserved serine residues in their N-terminal adapter domains. HDAC7 regulates the effector programming of NKT cells in a manner that mirrors the function of PLZF. HDAC7 and PLZF inversely regulate a shared innate effector gene network that is highly relevant to autoimmune disease. HDAC7 nuclear export licenses innate effector development. HDAC7 serves as a gatekeeper of this developmental fate decision in the thymus
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). HDAC2_MOUSE
488
0
55302
Swiss-Prot
other Location (Reliability: 1)
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phosphoprotein
in thymocytes, TCR stimulation results in HDAC7 phosphorylation and nuclear exclusion via protein kinase D
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
generation of homozygous Hdac2-/- and heterozygous Hdac1-/+/Hdac2-/- isozyne HDAC2 knockout mutant oocytes, penotypes overview
additional information
-
generation of homozygous Hdac2-/- and heterozygous Hdac1-/+/Hdac2-/- isozyne HDAC2 knockout mutant oocytes, penotypes overview
additional information
-
knock-down of isoform HDAC2 expression by small hairpin RNA inhibits cellular proliferation in a dose-dependent manner, which is also partly p53-dependent and induces cellular senescence. Knock-down enhances p53-dependent trans-repression and trans-activation of a subset of target genes. Enhancement is due to increased p53-DNA binding activity
additional information
a gain-of-function HDAC7 mutant, HDAC7-DP, arrests thymic iNKT development, phenotype, overview. iNKT phenotype of HDAC7-DP transgenic mice, and of wild-type:HDAC7-DELTAP mixed hematopoietic chimeric mutants. The HDAC7-DELTAP transgenic population contributed robustly to the pool of CD4 and CD8 SP thymocytes, although there is a transient reduction in prevalence at the immature single positive (ISP) stage
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
the hepatic enzyme activity is significantly increased in nuclear and cytoplasmic fractions following partial hepatectomy. Isoform-specific effects of partial hepatectomy on isozyme HDAC mRNA and protein expression, with increased isozyme expression of the class I HDACs, 1 and 8, and class II HDAC4 in regenerating liver. Hepatic expression of (class II) HDAC5 is unchanged after partial hepatectomy, HDAC5 exhibits transient nuclear accumulation in regenerating liver
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
it is proposed that induction of Hsp70 and subsequent activation of HDAC2 are important triggering signals of cardiac hypertrophy
medicine
-
loss of class IIa HDACs in murine liver results in inhibition of FOXO target genes and lowers blood glucose, resulting in increased glycogen storage. Suppression of class IIa HDACs in mouse models of type 2 diabetes ameliorates hyperglycemia, suggesting that inhibitors of class I/II HDACs may be potential therapeutics for metabolic syndrome
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Harms, K.L.; Chen, X.
Histone deacetylase 2 modulates p53 transcriptional activities through regulation of p53-DNA binding activity
Cancer Res.
67
3145-3152
2007
Mus musculus
Hartman, H.B.; Yu, J.; Alenghat, T.; Ishizuka, T.; Lazar, M.A.
The histone-binding code of nuclear receptor co-repressors matches the substrate specificity of histone deacetylase 3
EMBO Rep.
6
445-451
2005
Mus musculus
Rossig, L.; Urbich, C.; Bruhl, T.; Dernbach, E.; Heeschen, C.; Chavakis, E.; Sasaki, K.; Aicher, D.; Diehl, F.; Seeger, F.; Potente, M.; Aicher, A.; Zanetta, L.; Dejana, E.; Zeiher, A.M.; Dimmeler, S.
Histone deacetylase activity is essential for the expression of HoxA9 and for endothelial commitment of progenitor cells
J. Exp. Med.
201
1825-1835
2005
Mus musculus
Geiger, R.C.; Kaufman, C.D.; Lam, A.P.; Budinger, G.R.; Dean, D.A.
Tubulin acetylation and histone deacetylase 6 activity in the lung under cyclic load
Am. J. Respir. Cell Mol. Biol.
40
76-82
2009
Homo sapiens, Mus musculus (Q9Z2V5), Mus musculus
Kee, H.J.; Eom, G.H.; Joung, H.; Shin, S.; Kim, J.R.; Cho, Y.K.; Choe, N.; Sim, B.W.; Jo, D.; Jeong, M.H.; Kim, K.K.; Seo, J.S.; Kook, H.
Activation of histone deacetylase 2 by inducible heat shock protein 70 in cardiac hypertrophy
Circ. Res.
103
1259-1269
2008
Mus musculus (P70288)
Knutson, S.K.; Chyla, B.J.; Amann, J.M.; Bhaskara, S.; Huppert, S.S.; Hiebert, S.W.
Liver-specific deletion of histone deacetylase 3 disrupts metabolic transcriptional networks
EMBO J.
27
1017-1028
2008
Mus musculus (O88895), Mus musculus
Wallace, D.M.; Cotter, T.G.
Histone deacetylase activity in conjunction with E2F-1 and p53 regulates Apaf-1 expression in 661W cells and the retina
J. Neurosci. Res.
87
887-905
2009
Mus musculus
Jawerka, M.; Colak, D.; Dimou, L.; Spiller, C.; Lagger, S.; Montgomery, R.L.; Olson, E.N.; Wurst, W.; Goettlicher, M.; Goetz, M.
The specific role of histone deacetylase 2 in adult neurogenesis
Neuron Glia Biol.
6
93-107
2010
Mus musculus
Mihaylova, M.M.; Vasquez, D.S.; Ravnskjaer, K.; Denechaud, P.D.; Yu, R.T.; Alvarez, J.G.; Downes, M.; Evans, R.M.; Montminy, M.; Shaw, R.J.
Class IIa histone deacetylases are hormone-activated regulators of FOXO and mammalian glucose homeostasis
Cell
145
607-621
2011
Mus musculus
Huang, J.; Barr, E.; Rudnick, D.A.
Characterization of the regulation and function of zinc-dependent histone deacetylases during rodent liver regeneration
Hepatology
57
1742-1751
2013
Mus musculus
Wong, J.C.; Tang, G.; Wu, X.; Liang, C.; Zhang, Z.; Guo, L.; Peng, Z.; Zhang, W.; Lin, X.; Wang, Z.; Mei, J.; Chen, J.; Pan, S.; Zhang, N.; Liu, Y.; Zhou, M.; Feng, L.; Zhao, W.; Li, S.; Zhang, C.; Zhang, M.; Rong, Y.; Jin, T.G.; Zhang, X.; Ren, S.; Ji, Y.; Zhao, R.; She, J.; Ren, Y.; Xu, C.; Chen, D.; Cai, J.; Shan, S.
Pharmacokinetic optimization of class-selective histone deacetylase inhibitors and identification of associated candidate predictive biomarkers of hepatocellular carcinoma tumor response
J. Med. Chem.
55
8903-8925
2012
Mus musculus (O09106), Mus musculus, Homo sapiens (Q13547)
Ma, P.; Schultz, R.M.
Histone deacetylase 2 (HDAC2) regulates chromosome segregation and kinetochore function via H4K16 deacetylation during oocyte maturation in mouse
PLoS Genet.
9
e1003377
2013
Mus musculus (P70288), Mus musculus
Kasler, H.G.; Lee, I.S.; Lim, H.W.; Verdin, E.
Histone deacetylase 7 mediates tissue-specific autoimmunity via control of innate effector function in invariant natural killer T cells
eLife
7
e32109
2018
Mus musculus (Q8C2B3), Homo sapiens (Q8WUI4), Homo sapiens, Mus musculus C57BL/6 (Q8C2B3)
EXTERNAL LINKS (specific for EC-Number 3.5.1.98)
Use of this online version of BRENDA is free under the CC BY 4.0 license. See terms of use for full details.
Release 2023.1 (January 2023)
Legal
Curated at
Member of
